Low-level X chromosome mosaicism in women with sporadic premature ovarian failure

Low-level X chromosome mosaicism and its clinical relevance are still under debate. It could be interpreted as a technical artefact, genuine mosaicism or as being age-related. This study evaluated the contribution of X chromosome mosaicism in phenotypically normal women with sporadic premature ovarian failure (POF). During 1999–2008, 114 patients with POF and 64 age matched controls were karyotyped. Thirteen patients (11.4%) had true X chromosome mosaicism (>10% of aneuploid cells) and 12 had (10.5%) low-level X-mosaicism (between 6–10% of aneuploid cells). The mean age of women with true and low-level mosaicism was 26.0 ± 5.65 years and 35.92 ± 3.87 years, respectively (P < 0.001). In the control group the incidence of cells with an abnormal number of X chromosomes was 1–3%. The results have practical implications for genetic counselling and fertility treatment. To search and confirm the low-level mosaicism, a higher number of metaphases should be analysed or additional fluorescence in-situ hybridization analysis must be performed. Although peripheral blood does not reflect the situation in ovarian tissue well, it is presumed that there are different aetiological causes for true and low-level X chromosome mosaicism. The possible causes and reproductive significance of low-level X chromosome mosaicism are discussed.X chromosome abnormalities are usually associated with abnormal sexual development and reproductive performance, such as amenorrhoea, infertility, recurrent abortions and premature ovarian failure. X chromosome mosaicism is the presence of two populations of cells in the body. Some cells have two X chromosomes while others have only one X chromosome. Low-level X chromosome mosaicism (less than 10% of cells have one X chromosome) and its clinical relevance are still under debate. It could be interpreted as a technical artefact, genuine mosaicism or as being age-related. We evaluated the contribution of X chromosome mosaicism in women with premature ovarian failure (POF). In the period between 1999 and 2008, the chromosomes of 114 patients with POF and 64 age matched controls were analysed. Thirteen patients (11.4%) had true X chromosome mosaicism (more than 10% of cells have one X chromosome) and 12 (10.5%) had low-level X chromosome mosaicism. The mean age of women with true and low-level mosaicism was 26.0 ± 5.65 years and 35.92 ± 3.87 years, respectively. In the control group the incidence of cells with an abnormal number of X chromosomes was 1–3%. We evaluated the contribution of true and low-level X chromosome mosaicism to POF in phenotypically normal women with sporadic POF by routine G-banding chromosome analysis of at least 50 metaphases. The results have practical implications for genetic counselling and fertility treatment. Although peripheral blood does not reflect the situation in ovarian tissue well, we presume that there are different aetiological causes for true and low-level X chromosome mosaicism.